Effect of Armagnac fractions on human platelet aggregation in vitro and on rat arteriovenous shunt thrombosis in vivo probably not related only to polyphenols.

UNLABELLED: Previous studies showed that alcohol-free extracts of Armagnac, an oak cask aged spirit rich in polyphenols, inhibit human platelet function in vitro and in vivo, in an experimental rat arteriovenous shunt thrombosis model and in human healthy volunteers. To identify active compounds, we fractionated a freeze-dried extract of a 10-year-old Armagnac using successively chloroform, diethyl ether and ethyl acetate. The 4 resulting fractions were tested on in vitro human platelet aggregation induced by ADP and in vivo on arteriovenous shunt thrombosis after 10 days oral treatment in rats. Active components were found mainly in fractions 1 and 3: at the highest concentration (2.4 10(-2) g/l), in vitro ADP-induced aggregation was inhibited by 62.7+/-2.1% and 51.2+/-3.8% for F1 and F3, respectively, vs 18.9+/-2.4% and 13.9+/-0.4% for fractions 2 and 4 and 33.6+/-1.5% for the crude extract. There was a significant decrease in thrombus weight with the crude extract and all fractions tested after 10 days treatment with 2.5 mg/kg/day orally, greatest with fraction 1. Characterisation of phenol content showed that fraction 1, the most biologically active, was essentially devoid of ellagic acid and ellagitannins, the polyphenols initially thought responsible for the effect, whereas fraction 2 which was mostly inactive, was the richest in polyphenols. CONCLUSION: The antiplatelet and antithrombotic activity of Armagnac seems mostly unrelated to polyphenols.

Extracts enriched in different polyphenolic families normalize increased cardiac NADPH oxidase expression while having differential effects on insulin resistance, hypertension, and cardiac hypertrophy in high-fructose-fed rats.

Insulin resistance and oxidative stress act synergistically in the development of cardiovascular complications. The present study compared the efficacy of three polyphenolic extracts in their capacity to prevent hypertension, cardiac hypertrophy, increased production of reactive oxygen species (ROS) by the aorta or the heart, and increased expression of cardiac NAD(P)H oxidase in a model of insulin resistance. Rats were fed a 60%-enriched fructose food and were treated once a day (gavage) for 6 weeks with 10 mL/kg of water only (F group) or the same amount of solution containing a red grape skin polyphenolic extract enriched in anthocyanins (ANT), a grape seed extract enriched in procyanidins and rich in galloylated procyanidins (PRO), or the commercial preparation Vitaflavan (VIT), rich in catechin oligomers. All treatments were administered at the same dose of 21 mg/kg of polyphenols. Our data indicate that (a) the ANT treatment prevented hypertension, cardiac hypertrophy, and production of ROS, (b) the PRO treatment prevented insulin resistance, hypertriglyceridemia, and overproduction of ROS but had only minor effects on hypertension or hypertrophy, while (c) Vitaflavan prevented hypertension, cardiac hypertrophy, and overproduction of ROS. All polyphenolic treatments prevented the increased expression of the p91phox NADPH oxidase subunit. In summary, our study suggest that (a) the pathogeny of cardiac hypertrophy in the fructose-fed rat disease involves both hypertension and hyperproduction of ROS, (b) polyphenolic extracts enriched in different types of polyphenols possess differential effects on insulin resistance, hypertension, and cardiac hypertrophy, and (c) polyphenols modulate the expression of NAD(P)H oxidase.

Red wine polyphenols alone or in association with ethanol prevent hypertension, cardiac hypertrophy, and production of reactive oxygen species in the insulin-resistant fructose-fed rat.

The effects of a red wine polyphenolic extract (RWPE), ethanol, or both combined were evaluated in insulin resistant rats. Rats were fed for 6 weeks with fructose (60%)-enriched food and force-fed with (a) water only (F group), (b) aqueous solution of RWPE (100 mg/kg, FP group), (c) 10% (v/v) mixture of ethanol and water (FE group), or (d) solution containing the same amount of the RWPE and ethanol (FPE group). Animals fed a standard chow (C group) were used for comparison purpose. After 6 weeks, blood pressure was higher in F (130.0 x b1 1.7 mm Hg) than in C animals (109.6 x b1 0.9 mm Hg) and similar to the C group in all other fructose-fed treatment groups. Relative heart weight was higher in F (3.10 x b1 0.05) than in C (2.78 x b1 0.07) and significantly lower in FP (2.92 x b1 0.04) and FPE (2.87 x b1 0.08 mg/g) than in F animals. Left ventricle and aorta productions of reactive oxygen species (O2*-) were higher in F than in C groups and lowered by the RWPE but not by the ethanol treatment. Ethanol but not the RWPE treatment reduced the degree of insulin resistance in the fructose-fed rats. In summary, our study showed that polyphenols are able to prevent cardiac hypertrophy and production of reactive oxygen species in the insulin resistant fructose-fed rat.